Department of Otorhinolaryngology, Head and Neck Surgery, Saarlandy University Medical Center, Homburg, Germany.
Department of Gynecology and Obstetrics, Saarland University Medical Center, Homburg, Germany.
Front Immunol. 2023 Apr 18;14:1127576. doi: 10.3389/fimmu.2023.1127576. eCollection 2023.
Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients' quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology.
Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-Grunwald-Giemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed.
In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-high-group showed a greater change of eosinophils over time (Δ17.82) compared to the Eo-low-group (Δ10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001).
Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method.
伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）是一种常见的慢性疾病，对患者的生活质量有很大影响。如果保守和手术指南治疗不能充分控制疾病负担，生物制剂可以被视为一种新的治疗选择，自 2019 年 Dupilumab 首次获批以来，它已经彻底改变了 CRSwNP 的治疗方法。为了选择从这种新治疗中获益的患者，并找到治疗监测的标志物，我们使用非侵入性鼻拭子细胞学研究了患有 CRSwNP 并接受 Dupilumab 治疗的患者的鼻腔黏膜和炎症细胞的细胞组成。
本前瞻性临床研究纳入了 20 名符合 Dupilumab 治疗指征的 CRSwNP 患者。总共进行了 5 次门诊鼻腔差异细胞学检查，从开始治疗时使用鼻拭子进行，随后每 3 个月进行一次，共 12 个月。首先，这些细胞学样本用梅-格伦瓦尔德-吉姆萨法（MGG）染色，分析纤毛细胞、粘蛋白细胞、嗜酸性粒细胞、中性粒细胞和淋巴细胞的百分比。其次，进行免疫细胞化学（ICC）ECP 染色以检测嗜酸性粒细胞粒细胞。此外，在每次研究访问期间，记录鼻息肉评分、SNOT20 问卷、嗅觉测试、外周血总 IgE 浓度以及外周血嗜酸性粒细胞计数。评估一年中的参数变化，并分析临床疗效与鼻腔差异细胞学之间的相关性。
在 MGG（p<0.0001）和 ICC 分析（p<0.001）中，Dupilumab 治疗后嗜酸性粒细胞明显减少。当根据第一次研究访问中鼻拭子细胞学中嗜酸性粒细胞的百分比将患者分为 Eo-低（<21%）和 Eo-高（≥21%）组时，Eo-高组的嗜酸性粒细胞变化更大（Δ17.82）与 Eo-低组（Δ10.67）相比，但治疗反应没有更好。在观察期间，息肉评分、SNOT20 问卷和外周血总 IgE 浓度均显著下降（p<0.0001）。
鼻拭子细胞学作为一种易于应用的诊断方法，可以在特定时间检测和定量鼻腔黏膜中的不同细胞群。Dupilumab 治疗期间，鼻差异细胞学显示嗜酸性粒细胞显著减少，因此可作为该昂贵治疗的监测治疗效果的非侵入性方法，并可能允许对 CRSwNP 患者进行个体化治疗计划和管理的优化。由于我们的研究中初始鼻拭子嗜酸性粒细胞计数作为治疗反应预测生物标志物的有效性有限，因此需要进行包括更多参与者的进一步研究，以进一步评估这种新诊断方法在临床实践中的潜在益处。
